1218 J. Org. Chem., Vol. 43, No. 6, 1978
Abramovitch et al.
Intramolecular Cyclizations of Diphenyl Ether, Benzophenone, and Related 2-Sulfonylnitrenesla Rudolph A. Abramovitch,*lb Christopher I. Azogu, Ian T. McMaster, and Danny P. Vanderpool Department of Chemistry, liniversity of Alabama, University, Alabama 35486, and University of Saskatchewan, Saskatoon, Saskatchewan, Canada Receiued J u n e 22. 1977 Thermolysis of 2-phenoxybenzenesulfonylazide gave 6H-dibenzo[b,f][1,4,5]oxathiazepine 5,5-oxide (4) (the first seven-membered ring compound formed by intramolecular aromatic cyclization of a sulfonylnitrene) and other nitrene-derived products. On the other hand, diphenyl sulfide 2-sulfonyl azide (lb) gave some 3-phenylbenzo[l,3,2]dithiazolium ylide 1,l-dioxide (lo),but no seven-membered ring compound. Thermolysis of diphenyl sulfone 2-SUIfonyl azide gave only small amounts of products derived from the aryl radical 16, but no nitrene-derived compounds. Decomposition of 2-azidosulfonylbenzophenonesgave the desired seven-membered sultams without rearrangement, together with an array of other products. Some of these are formed from the sulfonylnitrene, while it is proposed that the others result from ring-chain tautomerization of some undecomposed sulfonyl azide to 3-aryl3-azidobenzo[d][2,1]oxathioles (34). Decomposition of the latter to the alkylnitrene and 1,2-aryl shifts would account for the products observed.
In earlier papers, the intramolecular cyclization of 2-biarylsulfonyl azides2 and the intramolecular insertion of arylsulfonylnitrenes into aliphatic side chains3 were described. A variety of five- and six -membered sultams was obtained and a number of important side reactions were noted and discussed. The present paper describes work aimed a t synthesizing seven-membered sultams by intramolecular cyclization of appropriate ortho-substituted arylsulfonylnitrenes and discusses the scope and limitations of some of these reactions. At the time this work was initiated direct intramolecular cyclization of a nitrene to a seven-membered ring was unprecedented. Since then a number of examples (rings formed indirectly, however) have been recorded.4 A. Decomposition of 2-PhenoxybenzenesulfonylAzide ( l a ) . The azide was thermolyzed in n-dodecane at 130-135 “C to give N-dodecyl-2-phenoxybenzenesulfonamide (2) (1%;
‘SO,NHR
SC).S
la,X=O b.X=S c. x = so, d. X = NCOCH,,4,4’-Me2 e. X = CO
2, = C 1 2 H 2 5 3,R=H
S0,X
‘SO,Ph
5, x = c1 7, X = N H C , , H 2 , 8, X = NH,
6
(4%) diphenyl sulfoxide 2-sulfonamide (9) and 3-phenylbenzo[1,3,2]dithiazolium ylide 1,l-dioxide (10) (10%). Again, Ph
Ph
I
I
10
9
a better yield (28%)of 10 was obtained when the reaction was carried out in the absence of solvent. The sulfoxide 9 undoubtedly arises by hydrolysis of 10 during workup and, indeed, chromatography of 10 on neutral alumina gave 9, as did basic hydrolysis of 10. Authentic 10 could be prepared from 8 and bromine in aqueous methanol, with or without added base. On the other hand, bromination of 8 in chloroform a t room temperature gave a mixture of 2- and 4-bromodiphenyl sulfide 2’-sulfonamide (1 1). Treatment of 10 with dimethyl sulfate and KOH gave diphenyl sulfide 2-N,N-dimethylsulfonamide (12), also obtained by the methylation of 8.
4
a mixture of isomers resulting from insertion of the nitrene into the solvent) and the hydrogen-abstraction product 3 (4%,), together with the desired cyclization products 6H-dibenzo[b,f][1,4,5]oxathiazepine5,5-dioxide (4)(15%).A better yield of 4 was obtained (38%)by carrying out the thermolysis in the absence of solvent. B. Decomposition of Diphenyl sulfide 2-Sulfonyl Azide (1 b). This azide was prepared as usual from the corresponding sulfonyl chloride 5. When benzene was used as the solvent in the synthesis of 5 from the primary amine and the reaction mixture was warmed to 40 “C instead of being kept at room temperature, acylation of the solvent occurred and 2-phenyl thiodiphenyl sulfone (6 1 was isolated. No seven-membered ring product was isolated on thermolysis of l b in n-dodecane at 150 “C. Instead there were obtained the solvent insertion (7) and hydrogen-abstraction (8) products, together with some
11
12
In view of the fact that both C-H insertion and hydrogenabstraction products were obtained, indicating the intermediacy of a free sulfonylnitrene in these reactions, it seems likely that 10 is formed by nucleophilic trapping of the sulPh
I
0022-3263/78/1943-1218$01.00/0 01978 American Chemical Society
Ph
I
J . Org. Chem., Vol. 43, No. 6, 1978 1219
Cyclizations of :!-Sulfonylnitrenes Table I. Thermolvsis Products of la-d Registry no.
Compd
Temp, "C
Time, h
40182-15-8
la
130-135 165 150 160- 170 150 150 160
30
la
64939-38-4
lb lb IC
64939-39-5
IC
le
Solvent
Yield of products
n-Dodecane
2 (11%), 3 (4%),4 (15%)
3 (59.9961,4 (37.9%) 7 (8.8%),8 (19%),9 (4%),10 (10%) 9 (26%),10 (27%) 13 (27%), 14 (9%) 13 (19%),14 (19%) 14 (1.9%),15 (2.6%)
12
61 3 16 16 18
(%)
n-Dodecane n-Dodecane n-DodecanelSa FreonE-4
Table 11. Thermolysis Products of Benzophenone-2-Sulfonyl Azides % yield of Productsn
Registry no. 63113-42-8
63113-43-9
63113-44-0
Temp, C"
Time, h
le
100
120
le
140
48
le le 23
l$O 100 100
48 120 120
23
140
10
24
140
18
ComDd
Solvent
Starting azide
17
18
19
20
21
35
3.5
15
1
1
1
2
1
Freon 113 Freon 113 CGHSC1 EtOH Freon 113 Freon 113 Freon 113
3 7
2
40 43
3 5
20
15
6
6
3
5
26
27
4
2 4
25
3
2
4
trace 1
26 33 40
Corrected for recovered azide. fonylnitrene by the sulfur atom rather than by participation of the latter in the nitrogen e l i m i n a t i ~ n . ~ C. Decomposition of Diphenyl Sulfone 2-Sulfonyl Azide (IC). In order to prevent this nucleophilic attack by sulfur on nitrogen, the decomposition of I C was studied. In this case, again no seven-membered ring product was detected. Thermolysis in n-dodecane at 150 "C gave diphenyl sulfone (13) (27%) and diphenyl sulfone 2-sulfonamide (14) (9%), both identical with authentic samples. Decomposition in Freon E-4 at 160 "C gave dibenzothiophene 5,5-dioxide (15)and 14, both in very low yields. Much tar was formed. While the hydrogen-abstraction product (14) probably arises from the triplet nitrene we propose that both 13 and 15 are formed from the corresponding aryl radical 16. Evidence for the formation of PhS0,Ph
+
o(
S02Ph SO,",
13
14
15
16
alkyl and aryl radicals in the thermolysis of some sulfonyl azides has been summarizeda6For example, it has been shown that a small amount of n-pentane was formed in the decomposition of n-pentanesulfonyl azide in mineral oil and that aromatic sulfonyl azides can undergo free-radical thermal decomposition if a source of radicals is provided.2,5v7Diphenyl sulfone (13) would result from 16 by hydrogen abstraction from solvent, while in Freon E-4 where hydrogen atoms are not available Pschorr-type cyclization occurs to give 15. That no seven-membered ring product is formed from IC might be due to a rapid intersystem crossing of singlet to triplet nitrene in this instance, or to an unfavorable geometry imposed by the
relatively large SO2 bridging group. The ease of Pschorr-type cyclizations in related systems has similarly been attributed to the internuclear separation between the rings involved as determined by the nature of the bridging group.* A similar attempt to effect the cyclization of N-acetyldip-tolylamine 2-sulfonyl azide (la)in dodecane did not yield any of the desired product; only the thermally unstable solvent insertion products were isolated. The results of the thermolyses of azides la-d are summarized in Table I. D. Decomposition of 2-Azidosulfonylbenzophenones. The decomposition of 2-azidosulfonylbenzophenone (le)was much more productive. A low yield of the desired sultam 17a was obtained (3.5%)together with some orthanilic acid (18a) (15%) and small amounts of 3-phenylbenzisothiazole 1,ldioxide (19a), 2-phenylbenzisothiazolin-3-one1,l-dioxide (20a), and benzanilide (21). The structure of the sultam 17a was supported by its infrared spectrum (v" 3200, UC=O 1640, vson 1350, 1180 cm-l) and by the synthesis of an authentic sample of its N-methyl derivative 22 from methyl anthranilate (Scheme I). Sultam 22 was identical with the product obtained on methylation of 17a with sodium hydride and dimethyl sulfate. The benzisothiazole 19a was identical with an authentic sampleagThe isothiazolinone 20a [IR 1730 (CO), 1335, 1185 cm-' (SOz)]could be synthesized from the N,2-dilithio derivative of benzenesulfonanilide by carbonation.10 In order to determine whether or not any rearrangements via a spiro intermediate" had occurred and to throw light on the formation of 21a, the decompositions of 4'-methylbenzophenone-2-sulfonyl azide (23) and 5-methylbenzophenone-2-sulfonyl azide (24) were investigated. The results are summarized in Table 11, and the nature of the products obtained is outlined in Scheme 11. The sultam 17b from the decomposition of 23 was N-ethylated to give 28. If a rearrangement via a spiro intermediate in the cyclization step had occurred (Scheme 111)then sultam 29 could have resulted. The N-ethyl derivative of the latter was prepared as described in Scheme I except that N-ethyl-p-toluidine was used in lieu of N-methylaniline. The product obtained was different from
1220
J . Org. Chem,, Vol. 43, No. 6, 1978
Abramovitch et al.
Scheme I
Scheme I11 C0,Me
I 'raNO,, -!I
C,&NHMe*
HCI
!10 CuCI, AcOH
e;l-'"l"'
S0,CI CO,H aq
S02NC,H,
1
I
Me
(yQ
Me
0 I
PcL
o,s--r\r
Me
LAH
cs
1
1
___)
11
fl
MeOH
l , S' O ' NC,H
AlCl
0,s-NMe 22
L 2-CO shifr
Qy=J
Scheme I1
O ? S -H
Me
&Me 0,s-N
s.
28
0,s- NH
R '
so?N
'R
17a, R = R' = H b, R = M e ; R' = H c, R = H; R = Me
l e , R = R' = H 23, R = M e , R' = I-[ 24, R = H.R = M P
H 29
20
+
R'
18 ,NHC'OC,H,R
so FI 26
25
+n R
@pM 0,s-A
0
I!)
0'
NHCOCGHiR
11 L1
P
underwent hydrolysis with remarkable ease: for example, attempted recrystallization from 95% ethanol gave 4-methylorthanilic acid ( 1 8 ~ )Thus, . the orthanilic acids obtained in those reactions arise from 26. This ease of hydrolysis is to be contrasted, say, with the hydrolysis of N,N- dicyclohexylbenzanilide-2-carboxamide in 1 M sulfuric acid at 80 "C for 6 h, which gave 2-benzamidobenzoic acid,13 indicating the stability of the latter o-carboxyamide under these much more drastic conditions. I t seems likely that intramolecular acid catalysis is responsible for the facile hydrolysis of 2Gc. Support for this comes from the observation of a broad carbonyl stretching band a t 1615 cm-l, indicating strong hydrogen bonding between the sulfonic acid and the ortho amide group.
tO?H 27
that formed on N-ethylation of 23, showing that no rearrangement had occurred. 3-p-Tolylbenzisothiazole 1,l-dioxide (19b)was prepared either from saccharin and p -tolylmagnesium bromideg or from ammonium 4'-methylbenzophenone-2-sulfonic acid (synthesized from o-sulfobenzoic anhydride and toluene with aluminum chloride; only one product isolated) and SOC12 or PC15, and was identical with the product obtained from the azide. Authentic 20b was prepared from o -sulfobenzoic anhydride and p-toluidine and then SOC12 as described,12 while 2Oc was made analogously to 20a. The thermolysis of 5-methylbenzophenone-2-sulfonylazide (24) was studied to determine the origin of 18,21, and 26. I t gave some 2-benzamido-4-methylbenzenesulfonicacid (26) as the major product, identical with an authentic sample, This
A small amount of N-benzoyl-rn-toluidide (21, R = €4; R' = Me) was also isolated in the thermolyses. Formation of these products indicates that the amino group bccupies the position originally bearing the carbonyl group ortho to the sulfonyl azide function. The usual small yield (6%) of seven-membered sultam 17c was also obtained. In the thermolysis of 4'-methylbenzophenone-2-sulfonyl azide (23) a t 140 "C in Freon 113, the main product (33%) obtained on careful workup was 3-(p-tolyl)benzo[c][2,1,4]oxathiazine 1,l-dioxide (25, R' = H). It exhibited a band a t 1633 cm-l consistent with an imidate C=N group,14 and bands a t 1360 and 1190 cm-1 (SOz). It underwent solvolysis
J . Org. Chem., Vol. 43, No. 6 , 1978
Cyclizations of 2-Sulfonylnitrenes
1221
Scheme IV
in ethanol readily to give orthanilic acid and ethyl p-methylbenzoate. An alternate structure considered for this product could be that of a /3-sultam (30, R = CH3). Some /3-sultams (31) similar to 30 have been postulated, but only one has been
34 -N
31
30
32
:k
chara~terized.'~ They are reported to cleave easily to the sulfene 32 and only when Ar is bulky can 31 be isolated. If, therefore, 30 were initially formed it would most likely rearrange to 25 (R' = H) via the sulfene corresponding to 32. Formation of 30 would, however, probably require insertion of a sulfonylnitrene into a position ortho to it and this has never been observed. Also, the frequency of the band observed at 1633 cm-l is somewhat lower than that observed for a tertiary aromatic amide, particularly when it is considered that the electron-withdrawing SO2 group on nitrogen is expected to raise the C==O stretching frequency by destabilizing the contributing structure -S02N+=C(-Q-)Ar. Assuming then that the compound has structure 25, it is possible to explain the array of products formed in these reactions by postulating two competing processes. Thermolysis with loss of nitrogen to give the sulfonylnitrene would account for the intramolecular cyclization products 17 and the 3-arylbenzisothiazole 1,l-dioxides (19); the latter arising by dehydration of the hydrogen abstraction products (33).10 It is
1
25
NC,H,R
KO/
CGH,Me
MeC,H,
N" \
0,s"
36
35
+
"'0:
COC,H,R -L+ HO
MeC,H,
19
SO,", 33
suggested that the other products arise by ring-chain tautomerization of some undecomposed sulfonyl azide (IC, 23, 24) to 3-aryl-3-azidobenzo[d][2,l]oxathioles (34). Decomposition of the latter to the alkylnitrene and 1,2-aryl shifts would give the observed products (Scheme IV), though a concerted nitrogen elimination aryl shift cannot be discounted.'6 Other mechanisms for the formation of the products are possible (e.g., 1,3-dipolar cycloaddition of the azide to the carbonyl group17J8to give 35 or 36 which, following cheletropic nitrogen elimination, would yield the oxaziridine 36 and thence on to the observed productlg), but are considered less likely since they would predict the product ratios to be inverted. Ring-chain tautomerism analogous to that proposed in Scheme IV has been reported often. Some examples include the tautomerization of o-benzoylbenzamide to aminophenylbenz~[c]oxoline,~~ of o-formylbenzoyl chloride to 3-chlorophthalide,21 of o-formylbenzenesulfonyl chloride to 3chlorobenzoxathiazoline,22of o-formylbenzenesulfonic acid to 3-hydro~ybenzoxathiole,~~ and of benzophenone-2-sulfonamides to 3-hydroxy-3-phenyl-2,3-dihydrobenzisothi~ole 1,l-di0xide.~4 The fact that no rearrangement was observed in the intramolecular cyclization here or in that of 4'-bromobiphenyl2-sulfonyl azide2 deserves some comment. Had spiro intermediates been involved in the formation of the final sultams then one might have expected to observe at least some rearranged products, which was not the case. If a spiro interme-
CsH,R
37
diate is indeed formed, then it is necessary to postulate that reversal to aziridine or [1,2] shift of nitrogen followed by a prototropic shift with aromatization is faster than the [1,2] shift of a carbonyl or aryl group. On the other hand, if the rearrangements observed by Cadogan and others with arylnitrenes involve first a concerted [02, ,2, .2,] shift to give an o-quinoid structure 38 (ppstulatedll to explain the for-
+
+
a;n
7then 1.3-H shift
V\y
[ J ,+
T2*
+ oA\
a;QJy -- QJ;ay 38
H
mation of other products) followed by a Cope-type cyclization, then the absence of rearrangements in the cases now under consideration is understandable, since concerted electrocyclic ring opening to an o-quinoid system is not possible in 39 and 40, and the only option available is ring opening to the unrearranged products.
Abramovitch et al.
1222 J . Org. P ' J i P m 3 Vol. 43, No. 6, 1978 /
R
and stirring was continued for 46 h. The mixture was concentrated with ether (3 X 25 mL), the combined extracts were dried (Na2S04), and the solvent was evaporated to give the azide (2.91 g, 100%)which, on attempted distillation, decomposed; IR (film) 2130 (s) ( N d , 1360, 1165 (s) cm-l (SO2).
Thermolysis of Diphenyl Sulfide 2-Sulfonyl Azide. A. In nDodecane. An emulsion of the azide (2.91 g) in n-dodecane (25 mL) 39
40
Experimental Section 2-PhenoxybenzenesulfonylAzide (la). Sodium azide (3.25 g) in water (25 mL) was added to a stirred solution of 2-phenoxybenzenesulfonyl chloride (13.4 g) in acetone (125 mL) and the solution was stirred a t room temperature for a further 27 h. It was evaporated in vacuo to about one-third of its volume and water (500 mL) was added. The precipitate (10.9 g, 7Yh) was filtered, washed with water (2 X 30 mL), and dried and had: mp 79-79.5 "C (from aqueous EtOH); IR (KBr) 2130,1360,1168cm-'. Anal. Calcd for CI2H9NaO3S:C, 52.35; H, 3.30; N, 15.26. Found: C, 52.26; H, 3.46; N, 1!5.41. Thermolysis of 2-Phenoxybenzenesulfonyl Azide. A. In nDodecane. A suspension 'of the azide (4.125 g) in n-dodecane (25 mL) was heated with stirring a t 130-135 "C for 30 h. The mixture was cooled to room temperature, the dodecane solution was decanted onto a column of neutral alumina (150 g) and the black tarry residue was extracted with boiling methanol (4 X 25 mL), and the extracts were evaporated, concentrated to 2 mL, and added to the alumina column. Elution with light petroleum gave n-dodecane. Elution with ether gave an almost colorless gum (0.972 g) which was distilled (some decomposition) to give slightly impure N-dodecyl-2-phenoxybenzenesulfonamide (2) as a yellow viscous liquid (0.696 g, 11%):bp 208 "C (0.2 mm); IR 3300, 1340, 1165 cm-l; NMR (CC14) 6 7.90-6.66 (m, ArH), 4.88 (d, 1, NH, exchangeable), 3.20 (m, 1, CHI, 1.40-0.70 (m, O ~417). S: 24); mass spectrum mil? 417 (M+-)(calcd for C Z ~ H ~ ~ NM+Elution with ether-methanol (955 v/v) gave 2-phenoxybenzenesulfonamide (3) (0.134 g, 4%) [mp 113-114 "C (from benzenelight petroleum); IR (KBri 3340,3240,1335,1165 cm-'] identical with an authentic sample prepared (76%) from sulfonyl chloride and ammonium hydroxide at room temperature. Anal. Calcd for CL2H11:VO?S: C, 57.84: H, 4.42: N, 5.62. Found: C, 57.72; H, 4.40; N, 6.li9. Elution with methanol ;gave a brown gum which, on crystallization from benzene, gave (iff-dibenzo[ b,fl[1,4,5]oxathiazepine 5,5dioxide (4) (0.571 g, 15%) mp 142-144 "C (aqueous EtOH); , , ,X 279 mm; IR (KBr) 3180, 1335, 1172 cm-l; mass spectrum m / e 247 (M'.). Anal. Calcd for C12HgNO3S: C, 58.29: H, 3.67: N, 5.67. Found: C, 58.32; H, 3.66; N, 5.75. B. In Absence of Solvent. The azide (0.70 g) was heated a t 165 "C for 12 h. The tarry products were chromatographed on a column of neutral alumina (30 g). Elution with light petroleum (bp 40-60 "C) gave 2-phenoxybenzenesulfonamide (0.19 g, 59.5% based on 2 mol of azide/mol of amide): mp 113-114 "C. Elution with methanol gave GN-dibenzo[b,f] [1,4.5]oxathiazepine5,5-dioxide (0.24 g, 37.9%): mp 136-139 "C. Diphenyl Sulfide 2-Sulfonyl Chloride (5). T o a solution of 2aminodiphenyl sulfide (20.1 g) in glacial acetic acid (140 mL) and concentrated HC1 (44 mL) at 0 "C was added a solution of sodium nitrite (8.0 g) in water (20 mL) at 0 "C. The diazonium salt solution of SO2 in glacial acet,ic acid (61 mL), ether (61 mL), and cupric chloride (5.0 g) was stirhd a t room temperature for 22 h. The solution was poured into ice-cold water (1500 mL) and the resulting yellow-orange solid was collected. washed with ice cold water (3 X 60 mL), and dried to give the sulfonyl chloride ( I 7.4 g, 61Oh):mp 54-54 "C (lit.25mp 53-45 "C), If benzene was used in the above reaction instead of ether and the reaction mixture was warmed a t 40 "C for 30 h instead of being kept a t room temperature for 22 h an oil mixed with needle-shaped crystals was obtained on pouring the mixture into water. The crystals (6 g) could be separated by taking advantage of their slight solubility in acetone. Recrystallization from benzene-methanol (1:l v/v) gave 2-phenyl thiodiphenyl sulfone (6): mp 123.5-125.5 "C; IR (KBr) 1445 ( s i , 1075 cm-I (m);mass spectrum mle 326 (M+.). Anal. Calcd for C1t%H1402S2: C, 66.27; H, 4.29. Found: C, 66.50; H, 4.42. Diphenyl Sulfide 2-Sulfonyl Azide (lb). Sodium azide (0.65 g) in water (5.0 mL) was added to a stirred solution of diphenyl sulfide 2-sulfonyl chloride (2.85 g ) in acetone (25 mL) a t room temperature
was heated with stirring a t 150 "C for 61 h-The mixture was cooled, the dodecane was decanted onto a column of neutral alumina (140 g), and the residual black tar was extracted with boiling MeOH (4 X 25 mL). The combined extracts were concentrated to 2 mL and added to the above alumina column. Elution with light petroleum gave n dodecane. Elution with ether-light petroleum (1:l v/v) gave a mixture of N-dodecyldiphenyl sulfide 2-sulfonamides (7) (0.397 g) as a yellow gum: IR (film) 3300,3060,2950,2920,2850,1320,1175cm-'; NMR (CDC13) 6 8-6.90 (m, 9, ArH), 5.55 (m, 1,exchangeable, NH), 3.18 (m, 1, CH), 1.40-0.7 (m, 24); mass spectrum m / e 433 (M+*). Elution with ether-methanol (19:l v/v) gave a yellow gum (0.875 g) which crystallized from ethanol-light petroleum to give diphenyl sulfide 2-sulfonamide (8) (0.504 g, 19%) [mp 111-112 "C; IR (KBr) 3380,3270,1340,1170 cm-l] identical with a sample prepared (76% yield) from the sulfonyl chloride and ammonia. Anal. Calcd for C12HllN02S2: C, 54.34; H. 4.15. Found: C. 54.60; H, 4.20. Further elution with the same solvent gave a yellow gum (0.176 g) which crystallized from ethanol to give diphenyl sulfoxide 2-sulfonamide (9) (0,101g, 4%): mp 155.5-156.5 "C; IR (KBr) 3310,3170, 1360,1184 cm-I. Anal. Calcd for C12HllN03S2: C, 51.25; H, 3.91. Found: C. 51.10; H, 4.00. Continued elution with ether-methanol gave a yellow gum (0.558 g) which crystallized from ethanol to give 3-phenylbenzo[ 1,3,2]dithiazolium ylide 1,l-dioxide (10) (0.274 g, 10%):mp 191-193 "C; (95% EtOH) 277.5, 270, 265, IR (KBr) 1293 (s), 1160 cm-I (s); A,, 230 nm (c 4632,3242,3367,14690);mass spectrum mle 263 (M+.). Anal. Calcd for C12HgN02S2: C, 54.71; H, 3.46. Found: C, 54.79; H, 3.78. B. In the Absence of Solvent. The azide (3.0 g) was heated under dry nitrogen a t 160-170 "C for 3 h. The dark product was chromatographed on a column of neutral alumina (90 9). Elution with benzene ylide 1.1-dioxide (0.75 g, 27%) gave 3-phenylbenzo[l,3,2]dithiazolium (mp 191-193 "C) identical with the sample obtained above and with an authentic sample (vide infra). Elution with methanol gave diphenyl sulfide 2-sulfonamide (0.36 g, 26%), identical with the product obtained above.
3-Phenylbenzo[ 1,3,2]dithiazolium Ylide 1,l-Dioxide (10). A. To a stirred solution of diphenyl sulfide 2-sulfonamide (1.325 g) in methanol (6 mL) and water ( 2 mL) was slowly added a solution of bromine (0.80 g) in methanol ( 2 mL) at room temperature. The solution was stirred for a further 20 min and poured into water (75 mL). The precipitated solid was filtered, washed with water, dried, and recrystallized from ethanol to give the ylide (1.034 g, 7%): mp 189-192 "C, undepressed on admixture with the above sample. The same product was obtained (69%; mp 191-192 "C) when the sulfonamide in 5 N NaOH was treated at 0 "C with a solution of bromine in methanol. B. Bromine (0.80 g) in CHC13 (5 mL) was added slowly to a stirred solution of the sulfonamide (1.325 g) in CHCl3 (15 mL) and the mixture was stirred at room temperature for 75 h. The solution was washed with water (2 X 20 mL), dried (Na2S04), and evaporated to give an orange-red gum (1.71 g) which was chromatographed on a column of neutral alumina. Elution with ether gave a colorless gun? (1.58 g) which crystallized from benzene to give what appears to be a mixture of 2- and 4-bromodiphenyl sulfide 2'-sulfonamide (11) [mp 91-94 "C; IR (KBr) 3420, 3360, 3290, 3250, 1330, 1175, 1170 cm-I; mass spectrum m / e (M+., 81Br),343 (M+., 79Br)l which could not be resolved. Diphenyl Sulfoxide 2-Sulfonamide (9). A. 3Phenylbenzo[l,3,2]dithiazoliumylide 1,l-dioxide (0.526 g) in ethanol (25 mL) and 20% aqueous NaOH (25 mL) was boiled under reflux for 13 h. The mixture was cooled, water (100 mL) was added, and the solution was acidified with concentrated HC1 and kept a t room temperature overnight. The solid was collected, washed with water (3 X 15 mL), dried, and recrystallized from ethanol to give the sulfoxide (0.313 g, 56%) (mp 155-157 "C) identical with the product obtained from the sulfonyl azide thermolysis. B. The ylide (0.526 g) in the minimum volume of CHC13 was chromatographed on a column of neutral alumina (150 g). The column was eluted with light petroleum and then allowed to stand for 3 days. Elution with ether-methanol (19:l v/v) gave unchanged ylide 10.266
Cyclizations of 2-Sulfonylnitrenes g): mp 191.5-193 "C. Elution with MeOH gave the sulfoxide (0.139 g, 26%) [mp 155-156 OC (EtOH)], identical with the above sample. Diphenyl Sulfone 2-Sulfonamide (14). Diphenyl sulfoxide 2sulfonamide (9) (0.281 g) in glacial acetic acid (2.0 mL) and 30% hydrogen peroxide (1.0 mI,) was heated a t 100 "C for 21 h. The cooled solution was poured into water (50 mL) and the solid which precipitated was recrystallized from ethanol to give diphenyl sulfone 2sulfonamide (0.151 g, 51%) (mp 162-163 "C) identical with a sample prepared from the sulfonyl chloride (see below) and ammonia: IR (KBr) 3360,3270,1345,1145 cm-l. Anal. Calcd for C12H~1N04S2:C, 48.48; H, 3.70. Found: C, 48.61; H , 3.82. Diphenyl Sulfide 2-N,N-Dimethylsulfonamide (12). A. 3Phenylbenzo[l.3,2]dithiazoliumylide 1,l-dioxide (10) (0.5 g) in absolute ethanol (5 mL) containing saturated aqueous KOH (15 mL) was stirred a t 60 "C as dimethyl sulfate (6 mL) was added dropwise. The mixture was then boiled under reflux for 6 h, cooled, and diluted with water until the white precipitate formed initially almost completely dissolved. The mixture was kept overnight and the diphenyl sulfide 2-N,N-dimethylsulfonamidewhich separated was recrystallized from a benzene--hexane mixture (1:4 v/v) (0.48 g, 81.7%):mp 118-119 "C; mass spectrum m/e 309 (M+.). Anal. Calcd f'or C14HL5N0&: C, 54.33; H, 4.89; N, 4.53. Found: C, 54.38; H, 4.70; N, 4.47. B. To a solution of diphenyl sulfide 2-sulfonamide (0.56 g) in EtOH (5 mL) containing 20% aqueous NaOH (15 mL) was added slowly with shaking dimethyl sulfate (6 mL) and the solution was boiled under reflux for 13 h. Workup as above gave the N,N-dimethyl derivative (0.34 g, 55%): mp 121-122 "C. Diphenyl Sulfone 2-N,N-Dimethylsulfonamide. The sulfoxide (0.31 gj in glacial acetic acid (2.0 mL) and 30% H202 (1.0 mL) was heated at 100 "C for 17.5 h. The mixture was cooled and poured into water (50 mL). The precipitated solid was filtered, washed with water (3 X 10 mL), and recrystallized from benzene-light petroleum to give the sulfone (0.20 g, 63%) [mp 148-149 "C (EtOH)] identical with a sample prepared (55%)from the sulfonyl chloride and dimethylamine: IR (KBr) 1320, 1310, 1170,1160 cm-'. Anal. Calcd for C14H15N04S2:C, 51.69; H, 4.62. Found: C, 15.91; H, 4.61. Diphenyl Sulfone 2-Sulfonyl Chloride. A solution of 2-aminodiphenyl sulfonez6 (2.33 g) in glacial acetic acid (7.0 mL) and concentrated HC1 (2.2 mL) a t 0 "C was treated with sodium nitrite (0.8 gj in water (2.0 mL). The diazonium salt solution was poured into an ice cold mixture of a saturated solution of SO2 in glacial acetic acid (6.1 mL), benzene (6.1 mL), and cupric chloride (0.5 g), and the mixture was stirred at room temperature for 16 h. It was poured into water and the yellow solid which precipitated was filtered, washed with water, dried, iind recrystallized from ethyl acetate-light petroleum to give the sulfonyl chloride (2.68 g, 85%):mp 137-138 "C; IR (KBr) 1370,1310,1150 cm-I. Anal. Calcd for C12HgC104Sz:C, 45.50; H, 2.84. Found: C, 45.81; H, 2.90. Diphenyl Sulfone 2-Sulfonyl Azide ( I C ) . Sodium azide (1.30 g) in water (10 mL) was added to a stirred solution of diphenyl sulfone 2-sulfonyl chloride (8.31 g) in acetone (50 mL) a t room temperature and stirring was continued for 16 h. The solution was concentrated in vacuo down to 15 mL togive the azide as an oil which solidified (6.34 g, 85%): mp 99.5-100 'C (ethanol-light petroleum); IR (KBr) 2150, 1340,1205,1180 cm-'. Anal. Calctl for C12H9N304S2:C, 44.56; H, 2.79. Found: C, 44.62; H , 2.91. Thermolysis of Diphenyl Sulfone 2-Sulfonyl Azide. A. In nDodecane. A suspension of diphenyl sulfone 2-sulfonyl azide (1.615 g) in n-dodecane (25 mL) was heated with stirring a t 150 "C for 16 h. The reaction mixture was cooled and worked up as in the above cases. Elution of the alumina column with light petroleum gave first n dodecane and then diphenyl sulfone (13) (0.297 g, 27%) (mp 125 "C) identical (mixture melting point and infrared spectrum) with an authentic sample. Elution with MeOH gave a dark brown gum (0.381 g) which was extracted with benzene (10 mL), filtered, and concentrated down to -1 mL to give diphenyl sulfone 2-sulfonamide (14) (0.138 g, 9%) (mp 159-160 "C) identical with an authentic sample. When this thermolysis was repeated but in the presence of sulfur (0.128 g), diphenyl sulfone (0.203 g, 19%) and diphenyl sulfone 2sulfonamide (0.287 g: 19%) were isolated. B. In Freon E-4. A suspension of the azide (0.969 g) in Freon E-4 (15 mL) was heated with stirring a t 160 "C for 18 h. The cooled mixture was worked up as usual. Elution of the column with ether gave a brown gum (0.062 g:I which gave dibenzothiophene S,S-dioxide (15) as colorless needles (0.002 g) [mp 232-233 "C from EtOH; IR (KBr)
J . Org. Chem., Vol. 43, No. 6, 1978
1223
1295,1170,1160 cm-l] identical with an authentic sample.27Elution with methanol gave diphenyl sulfone 2-sulfonamide (14) (0.002 g), identical with an authentic sample. N-Acetyldi-p-tolylamine 2-Sulfonyl Chloride. N-Acetyldip-tolylamine (1g) (mp 84-85 "C) was dissolved in CHC13 (5 mL) and the solution cooled in ice. Chlorosulfonic acid (5 mL) was added dropwise with stirring and the solution was kept at room temperature for 1h. It was then poured onto crushed ice and the CHC13 layer was separated, washed with cold water, dried (MgS04), and evaporated to give the sulfonyl chloride (1.09 g, 77.2%): mp 133.5-134.5 "C (from light aetroleum containing a few drops of CHCla); IR (KBr) 1665 (s), 13651s), 1170 cm-' (s). Anal. Calcd for C16H1&1N03S: C, 56.85; H, 4.78. Found: C, 56.43; H, 4.84. N-Acetyldi-p-tolylamine 2-Sulfonyl Azide (Id). The sulfonyl chloride (0.14 g) in acetone (20 mL) was treated at 0 "C with a solution of sodium azide (0.5 g) in the minimum amount of water. After stirring the solution at 0 "C for 1h it was diluted with water (200 mL) and the precipitated azide (0.13 g, 91.1%) was recrystallized from n-hexane to give colorless crystals: mp 94-95 "C; IR (KBr) 2118 (s), 1670 (s), 1170 cm-' (s). Anal. Calcd for C ~ ~ H I ~ N C, ~O 55.77; ~ S H, : 4.69. Found: c, 55.79; H, 4.93.
Thermolysis of N-Acetyldi-p-tolylamine 2-Sulfonyl Azide in n-Dodecane. The azide (1.0 g) in degassed n-dodecane (10 mL) was heated a t 160-170 "C for 6 h with stirring. Workup as usual and chromatography on neutral alumina gave, on elution with light petroleum (bp 40-60 "C), a mixture of the N-acetyldi-p-tolylamine N'-dodecyl-2-sulfonamidesas a brown oil (0.3 g) which could not be crystallized or distilled without decomposition: IR (film) 3280 (NH), 1650 (CO), 1315, 1150 cm-l (SO*): mass spectrum m/e (re1 intensity) 486 (M+., 8 ) , 239 (M+. - S02NHC12H25, 36), 197 (Ci4Hi5N+, 100). BenzoDhenone-2-sulfonyl Azide ( l e ) .This was prepared (0.4 g, 70%) from the sulfonyl chloride28 (0.6 gj in acetone (25 mL) with sodium azide (1g) in water (6 mL): mp 120-121 "C (hexane); IR (KBr) 2140,1660,1375, 1190 cm-l. Anal. Calcd for C13HgN303S: C, 54.35; H. 3.16; N, 14.63. Found: C, 54.28; H, 3.32; N, 14.89.
Thermolysis of Benzophenone-2-sulfonyl Azide. A. In Chlorobenzene, The azide (1g) in chlorobenzene (50 mL) was heated at 150 "C for 2 days. The black residue on evaporation of the solvent was resolved by preparative TLC (silica gel, benzene developer) to give: (i) 3-phenylbenzoisothiazole 1,l-dioxide (19, R = R = H) (19 mg, 2%) [mp 167 "C, mass spectrum m/e 243 (M+-)]identical (mmp and IR) with an authentic samp1e;g (ii) benzanilide (21, R = R' = H) (30 mg, 4%) (mp 160-161 "C) identical with an authentic sample; (iii) 11oxo-6H-dibenzo[c,fJ[1,Zlthiazepine 5,5-dioxide (17a) (60 mg, 7%) [mp 214-215 "C; IR (KBr) 3200,1635,1345,1290,1180 cm-I; mass spectrum m/e 259 (M+.)]. Anal. Calcd for C13HgN03S: C, 60.22; H. 3.50. Found: C, 60.12; H, 3.50. This (20 mg) was treated with sodium hydride (10 mg) in T H F (1 mL) and dimethyl sulfate (0.3 mL) was added. After 12 h a t room temperature the mixture was filtered and the solvent was evaporated thiazepine 5,5-dioxide to give 6-methyl-ll-oxo-6H-dibenzo[c,f][1,2] (22) (20 mg, 90%) [mp 159-160 "C (absolute EtOH)] identical with authentic material (vide infra). B. In Freon 133 at 100 "C.The azide (1.0g) in Freon 113 (50 mL) was heated for 5 days a t 100 "C in a sealed tube. The solvent was evaporated and ethanol (10 mL) was added to precipitate orthanilic acid (60 mg, 15%) (mp > 250 "C dec), identical (IR) with authentic material. The ethanol was evaporated and the residue was resolved by preparative TLC (silica gel, benzene developer) to give: (i) recov1,lered azide (332 mg, 35%); (ii) 2-phenylbenzoisothiazolin-3-one dioxide (4 mg, 1%)[mp 186-187 "C (EtOH); IR (KBr) 1735,1725, 1340,1300,1185cm-1; mass spectrum m / p 259 (M+-)]identical with an authentic samp1e;'O (iii) 3-phenylbenzoisothiazole1,l-dioxide (5 mg, 1%)(mp 165-167 "C) identical with an authentic sample; (iv) ll-oxo-6H-dibenzo[c,~][1,2]thiazepine 5,5-dioxide 132 mg, 3.5%) (mp 213-214 "C); (v) benzanilide (7 mg, 1%)(mp 160'161 "C). C. In Freon 113 at 140 "C. Thermolysis of the azide (2.0 g) in Freon 113 a t 140 "C for 2 days gave: (i) 2-phenylbenzoisothiazolin-3-one 1,l-dioxide (20) (14 mg, 1%); (ii) 3-phenylbenzoisothiazole1.1-dioxide (40 mg, 2%); (iii) ll-oxo-6H-dibenzo[c,f]11.21thiazepine 5,5-dioxide (54 mg, 3%). D. In Absolute Ethanol. The azide (0.8 g) in absolute ethanol (50 mL) was heated a t 100 "C for 5 days to give recovered azide (0.39 g, 40%), 3-phenylbenzoisothiazole 1,l-dioxide (82 mg, 20%), and 11oxo-6H-dibenzo[c,f][1,2]thiazepine 5,5-dioxide (17 mg, 3%).
1224 J . Org. Chem., Vol. 43, No. 6, 1978 Methyl Benzoate 2-PIT-Methylsulfonanilide.Methyl benzoate 2-sulfonyl chloride2g (I1,g) and N-methylaniline (5 mL) in pyridine (16 mL) were kept at room temperature for 30 min and water (50 mL) was then added. The precipitate was filtered and washed with 3% HCI (50 mLi and then with water (3 X 50 mL) to give the anilide (12.2 g, 90%): mp 93-94 "C (MeOH); IR (KBr) 1720,1340,1170cm-1; NMR (CDC13j6 7.3 (m, 9), 3.8 (s, 3, OCH3),3.3 (s, 3, NCH3); mass spectrum mie 305 (%I+.). Anal. Calcd for C15H151\J04S:C, 59.00; H, 4.95. Found: C, 58.98; H, 4.95. 6-Methyl-1 l-oxo-6H-~dibenzo[c,fl[ 1,2]thiazepine 5,5-Dioxide (22). The above anilide (12.1 g) was saponified with 30% aqueous methanolic (130 ml,) KOH (4.6 8). After 3 h a t 40 "C the mixture became homogeneous. Concentration afforded a white solid, a portion (6.2 g) of which was treated with PC15 ( 5 g) in carbon disulfide (200 mL) at 50 "C for 1 b, and then with anhydrous aluminum chloride (3.5 g) in nitromethane (6 mL). Heating was continued for 1h, the CS2 was decanted, and the red residue was treated with ice water (50 mL). The organic material was extracted with methylene chloride (100 mL), washed with 5% aqueous KOH ( 2 X 25 mL) and water (2 X 25 mLj, and dried (MgS04). Evaporation of the solvent gave the 6-methyl compound ( 2 g, 30%): mp 158-159 "C (absolute EtOH); IR (KBr) 1630: 1350,1180ern-': IVhlR (CDC13)6 8.25 (m, 1,ortho to SOz), 7.65 (m, 7 ) , 3.36 (s, 3, CH3); mass spectrum m / e 273 (M+-). Anal. Calcd for C14HllN03S: C, 61.52; H, 4.06. Found: C, 61.53; H, 4.07. 4-Methylbenzophenone-2-sulfonicAcid. A. 2-Amino-4'-methy l b e n z ~ p h e n o n e(7.2 ~ ~g) in acetic acid (20 mL) and concentrated HC1 (10 mL) was treated with sodium nitrite (2.8 g) a t 0 "C and the diazonium salt solution poured all at once into a cold saturated solution of SO2 in acetic acid (30 niL) and benzene (70 mL) containing copper(I1) chloride dihydrate (3 g). After 25 min at 25-30 "C (negative $-naphthol test) the dark green solution was poured into ice water (280 mL). The benzene layer was separated, the aqueous layer was extracted with ether ( 2 X 50 mL), and the combined organic layers were washed with wnter ( 3 X 50 mL), dried (MgS04), and concentrated to give an orange oil (10.1 9). This was treated with KOH (4 g) in water (100 mL) at 60 "C for 1 h. The aqueous phase was decanted and extracted with toluene (20 mL). Acidification and concentration of the water layer gave a semisolid which was treated with ethanol. The potassium chloride was filtered and the ethanol concentrated to give 4'-methylbenzophenone-2-sulfonic acid (5 g, 53%) as an oil: NMR (D20) 6 8.2 (dd, 1, ortho to SO*),7.5 (m, 71, 2.4 (s, 3, CH3). The acid was treated with KOH ( 5 g) in water (20 mL) to give potassium 4'methylbenzophenone-2-sulfonate(4 g,. 50%): mp 249-253 "C (lit.3' mp 248 "C). The alkali insoluble residue from the above reaction (3.9 g) was triturated with EtOH to give bis(4'-methyl-2-benzophenone)disulfide (1.6 g, 21%): mp 160-162 "C (from CH3CN); IR (KBr) 1640 em-': mass spectrum mlc 227 (M+./2); NMR (CDC13) 6 8.2 (m, 8),2.4 (s, 3). Anal. Calcd for CZ~H~:!O:!S~: C, 73.97; H, 4.88. Found: C, 73.77; H, 4.95. The ethanol filtrate gave bis(4'-methyl-2-benzophenone) disulfide S,S-dioxide (0.25 g, 3%): mp 115-116 "C (toluene); IR (KBr) 1650,1320,1280, 1265,1145ern-'; NMR (CDC13)6 7.5 (m, 17), 2.3 (d, 6, 2 CH3). Anal. Calcd for C ~ ~ H ~ Z O C,~69.11; S Z :H, 4.55. Found: C, 69.18; H, 4.46. B. Aluminum chloride (41 g) in nitromethane (43 mL) was added a t room temperature to o-sulfobenzoic anhydride32(30 g) in toluene (500 mL). A precipitate formed immediately. After 2 h the supernatent liquid was decanted. cold ammonium hydroxide (100 mL) was added to the solid, and the mixture was filtered. The solid was washed with EtOH, the combined filtrates were evaporated, and the residual syrup was treated with KOH (30 g) in water (250 mL) at 40 "C for 1 h. On cooling, potassium 4'-methylbenzophenone-2-sulfonateseparated as brownish crystals. Recrystallization from water (70 mL) gave pure sulfonate (30 g, 5990):mp 245-250 "C. 3-p-Tolylbenzoisothiazole 1,l-Dioxide (19, R = p-Me; R' = H). A. Ammonium 4 '-methylbenzophenone-2-sulfonate(5 g), prepared (syrup) as under B above, Wi3S heated with thionyl chloride (15 mL) in toluene (15 mL) at 100 "C for 7 h. Concentration of the solution afforded 3-~-tolylbenzoisothiazole 1,l-dioxide (3.9 g, 61%): mp 179-180 "C: (EtOH); IR (KElr) 1335,1175 cm-'; NMR (CF3C02H) 6 7.9 (m, 6), 7.45 (d, 2, J = E; Hz, half of an A2B2 quartet), 2.5 (s, 3, CH3); mass spectrum mle 257 (M+.). Anal. Calcd for C14HllNOzS: C, 65.34; H , 4.31. Found C, 65.24; H. 4.32. B. To saccharin (1.8 g) in dry T H F (200 mL) was added dropwise
Abramovitch e t al. a T H F solution of p-tolylmagnesium bromide [from p-bromotoluene (6.5 g) and magnesium (1.1g) in T H F (20 mL)]. After 2 days the solvent was evaporated and water was added to the residue. The mixture was filtered and solid was washed with water (25 mL) and then with ethanol-chloroform (1:l v/v; 3 X 25 mL). Concentration of the organic filtrates gave the product (1 g, 50%): mp 179-180 "C (CH3COzH). C. 4'-Methylbenzophenone-2-sulfonylchloride (2 g) in methanol (20 mL) was treated with ammonia for 2 h at room temperature. Evaporation of the methanol, washing the residue with water, and recrystallization from acetic acid gave the desired product (1 g, 60%): mp 179-180 "C. 4'-Methylbenzophenone-2-sulfonylAzide (23). Potassium 4'methylbenzophenone-2-sulfonate (33 g) and phosphorus pentachloride (28 g) were heated for 3 h a t 100 "C, ice water was added, and the mixture was extracted with methylene chloride (50 mL). The organic layer was washed with water (2 X 20 mL), dried (MgS04),and treated with tetramethylguanidinium azide (19 9). After 6 h the solution was washed with water (2 X 20 mL), dried (MgS04), and evaporated to give an orange oil (23 9). This was chromatographed on a column of silica gel (25 x 250 mm) and eluted with toluene (400 mL) to give the azide as an oil which crystallized from ethanol (8.1 g, 25%): mp 72-73 "C; IR (KBr) 2140, 1665, 1360, 1170 cm-I; NMR (CH3OD) 6 8.1 (m, 1, ortho to SOz), 7.7 (m, 71, 2.4 (s, CH3); mass spectrum mle 301 (M+.). Anal. Calcd for C14Hl1N303S: C, 55.80; H, 3.68; N, 13.94. Found: C, 56.05; H, 3.78; N, 13.50. Methyl Benzoate 2 4 N-Ethyl-N-(p-tolyl)]sulfonamide.Triethylamine (7.4 g) and N-ethyltoluidine (10 g) were added to an ether (200 mL) solution of methyl benzoate 2-sulfonyl chloride (17.0 9). After 12 h, triethylamine hydrochloride (9.8 g, 95%) was filtered. The ether was evaporated and the residue was recrystallized a t low temperature from MeOH to give the amide (18g, 75%): mp 54-56 "C; IR (KBr) 1730,1330,1290,1170,1150 cm-l; NMR (CDC13)6 7.4 (br, s, 4), 7.06 (s, 4), 3.90 (s, 3, OCH3), 3.74 (q, 2, J = 7 Hz, NCHz), 2.33 (s, 3, CH3), 1.08 (t, 3, J = 7 Hz, NCHzCH3); mass spectrum mle 333 (M+.). Anal. Calcd for C17H19N04S: C, 61.24; H, 5.74. Found: C, 61.27; H, 5.74. N-Ethyl-N-p-tolylbenzenesulfonamide-2-carboxylic Acid. The ester (4.8 g) in MeOH (10 mL) was saponified with NaOH (3.2 g) in water (171 mL) a t 60 "C for 3 h. The solution was made just acidic with concentrated HCI and the oil which separated was extracted with CHC13. Evaporation gave the acid (3.0 g, 65%):mp 119-120 "C (CC14); IR (KBr) 2600 (br), 1720 (m), 1630 (br s), 1345 (s), 1150 cm-I (sj; NMR (CDC13) 6 11 (br s, 1, COzH), 7.5 (m, 4), 7.1 (s,4), 3.7 (q, 2, J = 7 Hz, CHz), 2.3 (s, 3, CH3), 1.1 (t, 3, J = 7 Hz.CHBCCH~); mass spectrum mle 319 (M+.). Anal. Calcd for C16H17NO4S:C, 60.17; H, 5.36. Found: C, 60.20; H, 5.33. 6-Ethyl-9-methyl-1 l-oxo-6H-dibenzo[ c,fl[ 1,2]thiazepine 5,5-Dioxide. The above acid (1.0 g) and phosphorus pentachloride (0.91 g) in CS2 (20 mL) were boiled under reflux for 1 h, and then anhydrous aluminum chloride (0.3 g) was added. After heating for 1 h more, the solvent was evaporated and concentrated HCI (1 mL) and water (30 mL) were added. The oil was extracted with methylene chloride (60 mL) and the extract was washed with water (2 X 20 mL), dried (MgSOd),and evaporated to give an oil which, on treatment with methanol, gave the thiazepine dioxide (0.30 g, 32%): mp 154-155 "C (MeOH); IR (KBr) 1645,1345,1180ern-', NMR (CDC13) 6 7.7 (m, 7 ) , 3.7 (4,2, J = 7 Hz, NCHz), 2.3 (s, 3, CHB),0.99 (t, 3, J = 7 Hz, CHzCH3); mass spectrum mle 301 (M+.). Anal. Calcd for C16H1&%3S: C, 63.75; H, 5.02. Found C, 63.78; H, 5.02. Evaporation of the methanol mother liquors gave methyl benzoate 2-[N-ethyl-N-( p -tolyl)]sulfonamide (0.50 g, 48%). Thermolysis of 4'-Methylbenzophenone-2-sulfonylAzide (23). A. I n Freon 113 at 100 "C.The azide (0.643 g) in Freon 113 (40 mL) was heated for 5 days a t 100 "C in a sealed tube. The Freon was evaporated and chloroform was added to the black residue to precipitate orthanilic acid (73 mg, 35%) (mp >250 "C) identical (IR) with an authentic sample. The chloroform solution was added to the black residue to precipitate orthanilic acid (73 mg, 35%) (mp >250 "C) identical (IR) with an authentic sample. The chloroform solution was evaporated and the residual mixture was resolved by preparative TLC (silica gel, toluene developer) to give: (i) starting azide (0.278 g, 43%); 1,l-dioxide (20, R = p-Me; R' (ii) 2-(p-tolyl)benzoisothiazolin-3-one = H) (10 mg, 3%) [mp 198-199 "C; IR (KBr) 1730,1335,1305,1180; mass spectrum mle 273 (M+.)] identical with an authentic sample;12 (iii) 3-p-tolylbenzoisothiazole1,l-dioxide (19) (7.5 mg, 2%) (mp 177-179 "C) identical with the sample prepared above; (iv) 4-
Cyclizations of 2-Sulfonylnitrenes methylbenzanilide (21, R = Me; R' = H) (3 mg, 2%) [mp 145 "C; IR (KBr) 3280,1635 cm-1; mass spectrum m/e 211 (M+.)] identical with an authentic sample; (v) 8-methyl-ll-oxo-6H-dibenzo[ c,fl[ 1,2]thiazepine 5,5-dioxide (17b) (19 mg, 5%) [mp 235-236 "C (toluene); IR (KBr) 3190,1630,1340,1290,1185,1175cm-';NMR (acetone-&) 6 7.95 (d, 1,ortho to SOz), 7.75 (m, 5),7.08 (m, 2), 4.7 (br s, 1, exchanges with D20, NH), 2.36 (s, 3, CHd; mass spectrum mle 273 (M+.)]. Anal. Calcd for C14H11N03S:C, 61.52; H, 4.06. Found: C, 61.53; H, 4.08. The above sultam (2!i g) in T H F (1 mL) was treated with sodium hydride (10 mg) and then with diethyl sulfate (30 ILL).After 12 h a t room temperature the 'solution was filtered and evaporated to give 6-ethyl-8-methyl- 1l-oxo-6H-dibenzo[ c,fl[ 1,2]thiazepine 5,5dioxide (21 mg, 90%) [mp 118-119 "C (toluene-hexane); IR (KBr) 1640,1355,12&5,1243,1178 cm-'; NMR (CDC13) 6 7.90 (m, 5), 7.24 (m, 2), 3.84 (q, 1, J = '7 I-Iz), 2.45 (s, 3, CH3), 0.93 (t, 3, J = 7 Hz)]; this compound Wac different from the 6-ethyl-9-methyl derivative prepared above. Anal. Calcd for C16H15N03S:C, 63.75; H, 5.02. Found: C, 63.79; H, 5.02. (vi) p-Toluic acid (27, R = Me) (40 mg, 26%) (mp 176-178 "C) identical with an authentic sample. B. In Freon 113 at 140 "C. Thermolysis of the azide (1.67 g) in Freon 113 (40 mL) at 140 "C for 10 h gave a precipitate of 3-(ptolyl)benzo[c]j2,1.4]oxathiazine1,l-dioxide (25, R = Me; R' = H) (0.430 g, 33%): mp 144--146"C (from hexane); IR (KBr) 1633,1360, 1190; mass spectrum nile 273 (M+.). Anal. Calcd for C14HllN03S:C, 61.52; H, 4.06. Found: C, 61.28; H, 4.21. Treatment of this compound with ethanol gave orthanilic acid (18, R = H), identical with an authentic sample, and ethyl p-methylbenzoate [the latter was detected in the alcohol mother liquors by GLC on a column of 15% SE 30 on Chromosorb W at 152 "C, and identified by ils infrared spectrum (identical with that of an authentic sample)]. The Freon filtrate was evaporated and resolved by TLC (silica gel; toluene developer) to give: (i) recovered sulfonyl azide (0.256 g, 15%); (ii) 2-p-tolylt~enzoisothiazolin-3-one 1,l-dioxide (45 mg, 4%); (iii) 3-p-tolylbenzoisothiazole 1,l-dioxide (44 mg, 4%); (iv) 8-methyl1l-oxo-6H-dibenzo[c,,i][1,2]thiazepine 5,5-dioxide (80 mg, 6%); (v) a trace of 4-methylbenzanilide. Rechromatography of the material that had remained on the baseline usink CHC13 as eluent gave an unidentified compound (40 mg): mp 182-183 "C (EtOH);IR (KBr) 3240,1650,1340,1180 em-'; NMR (CDCl?) 6 7.9 (m, 6), 7.3 (m, 21, 2.7 (s, 3); mass spectrum mle 345 (M+. 4 for 35Cl),343 (M+. t 2), 341 (M+., 35Cl) (in the abundance ratio 1.7:6.1:9.0;calcd for 2 C1 1.0:6.0:9.0),309, 307 (abundance ratio 1.2:3.0; calcd for 1 C1 1.0:3.G). Anal. Found: C, 55.54; H, 3.67. 2-Benzamido-4-methylbenzenesulfonic Acid. Sodium 2 amino-4-methylbenzenesulfonate[from 2-amino-4-methylbenzenesulfonic acid33(0.5g) and an equivalent amount of aqueous NaOH followed by evaporation of the water] and benzoyl chloride (2 mL) were heated for 3 h at 100 "C and then for 30 min under reflux. The excess benzoyl chloride was distilled and the residue was extracted with hot acetonitrile. On cooling the benzamido derivative separated: mp 180-183 "C (from CH3CN); IR (KBr) 1620,1325,1190,1175 cm-'; mass spectrum mle 273 (M+. - 18). Anal. Calcd for C1&13N04S: C. 57.71; H, 4.50. Found: C, 57.57; H, 4.49. 5-Methylbenzophenone-2-sulfonyl Chloride. 2-Amino-5methylbenzophenone h y d r o ~ h l o r i d e(19 ~ ~g) in acetic acid (30 mL) and concentrated HCI(25 mL) was diazotized with sodium nitrite (7 g) in water (13 mL) m.d then added to a cold saturated solution of SOs in benzene (90 mL) and acetic acid (90 mL) containing CuClz (5 g). After 5 h at room temperature, the organic layer was separated, washed with water ( 5 X 50 mL), dried (MgSOd), and evaporated to yield an oil (-10.89). This was treated with acetic acid (100 mL), concentrated HC1 (20 mL), and potassium chlorate (5.8 g) in water (50 mL).35After 3 h at room temperature the solvent was evaporated, ethanol was added to the residual oil, and KCl(3.2 g, 91%) was separated. ConctntratiorL of the ethanol filtrate give 5-methylbenzop h e n o n e - 2 - d f o n i c acid (7.7 g, 36%) as a lime-colored syrup. The crude sulforic acid (7.7 g) was heated under reflux with thionyl chloride (20 mL) and DMF (0.5 mL) for 3 h and poured over ice (100 g) to give 5-methylbenzophenone-2-sulfonylchloride (6 g, 73%): mp 118-120 "C (EtOH); IR (KBr) 1670, 1360, 1170 cm-l; NMR (CDC13) 6 8.05(d, 1.J = 8 Hz. ortho to sulfonvl). 7.75 (dd. 2. J = 8 . 2 Hz, H3 and €Id),7.4 (in, 5, Ph), 2.5 (s, 3, CHs); mass spectrum mle 296 (M+., 3 7 ~ 1 1 ,294 m+..
J . Org. Chem., Vol. 43, No. 6, 1978
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Anal. Calcd For C14HllC103S: C, 57.04; H. 3.76. Found: C, 56.91; H, 3.73. 5-Methylbenzophenone-2-sulfonylAzide (24). This was prepared from the sulfonyl chloride (1.5 g) and tetramethylguanidinium azide (2 g) in CHC13 (30 mL) at room temperature for 12 h. The azide (0.52 g, 34%) h a d mp 97.5-99 "C (from toluene); IR (KBr) 2130,1675, 1360,1175 cm-'; NMR (CDC13) 6 7.95 (d, 1,J = 8 Hz, ortho to SO?), 7.65 (dd, 2 , J = 8, 2 Hz, H3 and H4), 7.4 (m, 5, Ph), 2.45 (s, 3. C H d ; mass spectrum mle 301 (M+.). Anal. Calcd for C14H11N303S: C, 55.80; H. 3.68. Found: C, 55.82; H, 3.69. Thermolysis of 5-Methylbenzophenone-2-sulfonyl Azide. The azide (1.17 g) in Freon 113 (60 mL) was heated for 18 h a t 140 "C in a sealed tube. The mixture was filtered from 2-benzamido-5-methylbenzenesulfonic acid (26, R = H; R' = Me) (0.42 g, 40%) [mp 183 "C (toluene or CHsCN)] identical with the authentic sample prepared above. This, on treatment with ethanol, gave 2-amino-5-methylbenzenesulfonic acid (18, R' = Me) identical with authentic material. The Freon filtrate was resolved by preparative TLC (silica gel, CHC13 eluent) to give: (i) benz-m-toluidide (21, R = H; R' = Me) (20 mg, 1%)(mp 125-126 "C) identical with an authentic sample; (This was shown to be a single isomer under conditions-microslide TLC, silica gel, methylene chloride development-suitable for the resolution of the m- and p-toluidides.) (ii) 2-methyl-11-oxo-6H-dibenzo[ c,fl[ 1,2]thiazepine 5,5-dioxide (17c) (64 mg, 6%): mp 203-204 "C (toluene); IR (KBr) 3200,1640,1350,1300,1180,1140cm-'; mass spectrum mle 273 (M+-). Anal. Calcd for C14HllN03S: C, 61.52: H, 4.06. Found: C, 61.43; H, 4.11. Treatment of this sultam (21 mg) in T H F (1mI,) with sodium hydride(5 mg) and diethyl sulfate (50 fiL) in T H F (1 mL) for 2 h a t 80 "C gave 6-ethyl-2-methyl- 1l-oxo-6H-dibenzo[ c,fl[ 1,2]thiazepine 5,5-dioxide (20 mg, 90%): mp 140-142 "C (MeOH);IR (KBr) 1655, 1345,1175 em-'. Anal. Calcd for C16H15NO3S:C, 63.75; H. 5.02. Found: C, 63.71; H, 5.02.
Acknowledgments. We wish to t h a n k the National Institutes of Health (NBO-8716 and GM-16626) and the National Science Foundation (MPS 75-09309) for grants i n support of this work (1970-1975) and the University of Alabama for the award of a Research Fellowship ( t o D.P.V.) (1970-1971).
+
w)
Registry No.-ld, 64939-40-8; 2, 64939-41-9; 3, 23393-41-1; 4, 22172-69-6; 5,2688-87-1; 6,64939-42-0; 7,64939-43-1; 8,22172-72-1; 9, 64939-44-2; 10, 22172-71-0; 11 (2-Br), 64939-45-3; 11 (4-Bu). 64939-46-4; 12, 22172-73-2; 13, 127-63-9; 14, 6462-14-2; 14 N,Ndimethyl, 64939-47-5;17a, 63113-45-1;17b, 63113-46-2; 17 (R = p-Me; R' = H), 38938-54-4; 20 (R, R' = H), 15449-00-0;21 (R, R' = H), 9398-1; 22, 26638-46-0; 25, (12 = p-Me; R' = H), 63113-48-4; sodium azide, 26628-22-8; 2-phenoxybenzenesulfonyl chloride, 2688-85-9; diphenyl sulfone 2-sulfonyl chloride, 6462-15-3; 2-aminodiphenyl sulfone, 4273-98-7; N-acetyldi-p-tolylamine, 32047-89-5; chlorosulfonic acid, 7790-94-5; N-acetyldi-p-tolylamine 2-sulfonyl chloride, 64939-29-3; N-acetyldi-p-tolylamine N'-dodecyl-2-sulfonamide, 64939-30-6; dodecane, 112-40-3; benzophenone-2-sulfonyl chloride, 54075-06-8; methyl benzoate 2-N-methylsulfonanilide, 26638-44-8; methyl benzoate 2-sulfonyl chloride, 26638-43-7; N-methyaniline, 100-61-8; 2-amino-4'-methylbenzophenone,36192-63-9; 4'-methylbenzophenone-2-sulfonic acid, 64939-31-7; potassium 4'-methylbenzophenone-2-sulfonate, 64939-32-8; his(4'-methyl-2-benzophenone) disulfide, 64939-33-9; bis(4'-methyl-2-benzophenone)disulfide S,Sdioxide, 64939-34-0; o-sulfobenzoic anhydride, 64975-68-4; ammonium 4'-methylbenzophenone-2-sulfonate,64939-35-1; p-bromotoluene, 106-38-7; 4'-methylbenzophenone-2-sulfonyl chloride, 64939-36-2; tetramethylguanidinium azide, 64939-37-3; methyl benzoate 2-[N-ethyl-N-(p-tolyl)sulfonamide, 64939-24-8; N-ethyltoluidine, 622-57-1; N-ethyl-N-p-tolylbenzenesulfonamide-2-carboxylic acid, 63113-54-2; 6-ethyl-9-methyl-1l-oxo-6H-dibenzo[c,fj[1,2]thiazepine 5,5-dioxide, 63113-52-0; diethyl sulfate, 64-67-5; 6ethyl-8-methyl-ll-oxo-6H-dibenzo[c,~][1,2[thiazepine5,5-dioxidr, acid, 63113-51-9; 63113-53-1; 2-benzamido-4-methylbenzenesulfonic 42876-65-3: benzoyl sodium 2-amino-4-methylbenzenesulfonate, chloride, 98-88-4; 2-amino-5-methylbenzophenoneHC1, 64939-25-9; 5-methylbenzophenone-2-sulfonic acid, 64939-26-0; 5-methylbenzophenone-2-sulfonyl chloride, 64939-27-1; 6-ethyl-2-methyl-11 oxo-6H-dibenzo[c,f][1,2]thiozepine5,5-dioxide, 64939-28-2.
1226 J . Org. Chem., Vol. 43, No. 6, 1978
Garnick, Levery, and Le Quesne
References and Notes
(15) M. S.Ao and E. M. Burgess, J. Am. Chem. SOC., 93, 5298 (1971). (16) Thermolysis of tertiary alkyl azides has been shown to involve the intermediacy of aikylnitrenes [R. A. Abramovitch and E. P. Kyba, J. Am. Chem. SOC.,$6, 480j1974)]. (17) R. A. Abramovitch, Chem. SOC.,Spec. Pub/., No. 24, 323 (1970). (18) J. H. Hall, F. E. Behr, and R. L. Reed, J. Am. Chem. SOC., 94, 4952 (1972). (19) W. D. Emmons in "Heterocyclic Compounds with Three and Four Membered Rings", Part 1, A. Weissberger, Ed., Interscience, New York, N.Y., 1964, p 624. (20) M. Ahmed and J. M. Vernon, J. Chem. SOC., Perkin Trans. 1, 2048 (1975). (21) M. Renson, Bull. SOC.Chim. Belg., 70, 77 (1961). (22) J. F. King, A. Hawson. 8. L. Huston, L. J. Danks, and J. Komery, Can. J. Chem., 49, 943 (1971). (23) K. A. Freeman and C. D. Ritchie, J. Assoc. Off. Agric. Chem., 40, 1108 (1957); Chem. Abstr., 52, 6067a (1958). (24) H. Watanabe, C.-L. Mao, I.T. Barnish, and C. R. Hauser, J. Org. Chem., 34, 919 (1969). (25) A. J. Neale, T. J. Rawlings. and E. B. McCall, Tetrahedron, 21, 1299 (1965). (26) F. Uilmann and G. Pasdemadjian, Ber., 34, 1150 (1901). (27) H. Gilman and D. L. Esmay, J. Am. Chem. SOC.,74, 2021 (1952). (28) J. B. Wright, J. Heterocycl. Chem., 5, 453 (1968). (29) H. Meerwein, G. Dittmar, R . Goellner, K. Haffner, F. Mensch, and 0. Steinfort, Chem. Ber., 90, 841 (1957). (30) H. J. Scheifele, Jr.. and D. F. de Tar, "Organic Syntheses", Collect. Voi. IV, Wiley. New York, N.Y., 1963, p 35. (31) C. Krannich, Ber., 33, 3485 (1900). (32) H. T. Clarke and E. E. Dreger, "Organic Syntheses", Collect. Vol. I, Wiley, New York, N.Y., 1958, p 495. (33) R . Hayduck, Justus Liebigs Ann. Chem., 174, 350 (1874). (34) D. A. Denton and H. Suschitsky, J. Chem. SOC.,4741 (1963). (35) To convert any disulfides and/or thiosulfonates to the corresponding sulfonic acid: H.V. Daeniker and J. Druey, Helv. Chim. Acta, 40, 2148 (1957).
(1) (a) For preliminary communications on some of this work see R. A. Abramovitch, C. I. Azogu, and I. T. McMaster, J. Am. Chem. SOC.,91, 1219 (1969). R. A. Abramovitch and D. P. Vanderpool, J. Chem. SOC.,Chem. Commun., 18 (1977). (b) Present address: Department of Chemistry and Geology, Clemson University, Clemson, S.C. 29631. (2) R. A. Abramovitch, T. Chellathurai, I. T. McMaster. T. Takaya, C. I. Azogu, and D.P. Vanderpool. J. Org. Chem., 42, 2914 (1977). (3) R. A. Abramovitch, T. Chellathurai, W. D. Holcomb, I. T. McMaster, and D. P. Vanderpool, J. Org. Chem., 42, 2920 (1977). (4) See, for example, I. M. McRobbie, 0. Meth-Cohn, and H. Suschitzky, J. Chem. Res. (S), 17 (1977), and references cited therein. (5) If sulfur participation were involved the thermolysis would be expected to take place at a temperature below that (-130-150 "C) at which unassisted decomposition takes place. The nitrene would be by-passed and hence, also, formation of 7 and 8, unless assisted and unassisted decompositions are delicately balanced. Formation of 10 rather than the sulfur analogue of 4 can be explained by the superior nucleophilicity of sulfur compared with the benzene ring toward the electrophilic singlet sulfonyinitrene. (6) R. A. Abramovitch and R . G. Sutheriand. Fortschr. Chem. Forsch., 16, 1 (1970). (7) D. S. Bresiow, M. F. Sloan. N. R. Newburg, and W. B. Renfrow, J. Am. Chem. Soc., 91, 2273 (1969). (8) D. H. Hey and R. D. Mulley, J, Chem. SOC., 2276 (1953). (9) R. A. Abramovitch, E. M. Smith, B. Purtschert, P. C. Srinivasan, and G. M. Singer, J. Chem. SOC. Perkin Trans. 1, 2590 (1974). (IO) H. Watanabe, R L. Gay, and C. R. Hauser, J, Org. Chem., 33, 900 (1968). (11) J. I. G. Cadogan, Acc. Chem. Res., 5, 303 (1972). (12) M. D. Sohon, Am. Chem. J., 20, 257 (1898). (13) T. Cohen and J. Lipowitz. J. Am. Chem. SOC.,88, 561 1 (1964). (14) (a) G. Hafelinger in "The (Chemistry of Amidines and Imidates", S. Patai, Ed.. Wiley, New Yo&. N.Y., 1975, pp 48-53; (b) 0. Y. Curtin and L. L. Miller, J. Am. Chem. Soc., 89, 637 (1967).
Addition and Annulation Reactions between Indoles and cw,P-Unsaturated Ketones Robert L. Garnick, Steven B. Levery, and Philip UT. Le Quesne* Department of Chemistry, Northeastern Uniuersity, Boston, Massachusetts 021 15 Receiued March 23,1977 The structure of the addition product formed by acid-catalyzed reaction between 1,3-dimethylindole and mesityl oxide is shown to be 12. Analogous products are formed with methyl vinyl ketone and benzalacetone as annulating agents. The reactions between methyl vinyl ketone and indole, 1,2-dimethylindole, and 3-methylindole are compared with these and with cyclization steps in the syntheses of the alkaloids villalstonine and vindorosine.
*
In a planned synthesi#sof strychnine Robinson and Saxton envisaged' the conversion of the dialdehyde 1 by a combination of Mannich and aldol-type condensations into the Wieland-Gumlich aldehyde 2, already known to be convertible into strychnine. The conversion 1 2 would have exemplified the concept of annulation utilizing electrophilic addition reactions of indoles. Subsequently, this concept has been realized in Buchi's synthesis of vindorosine,2 in which
-
a key step is the cyclization of the N-acetylenone 3 with boron trifluoride etherate into the indoline 4, and by our biomimetic synthesis of villalstonine (5) from macroline (6) and pleio-
p; H /
Pi-
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OHC HO'
1
I CH
\.
CH 1 CH 6
H H HO
H
2
CH,OOC
rn H
H
j
3
4
5
0022-326317811943-1226$01.00/0 0 1978 American Chemical Society
7
